The positron emission tomography (PET) is a branch of nuclear medicine in which the selected radiopharmaceutical is introduced into the body of a patient. PET radiopharmaceuticals comprise radioactive isotopes as e.g. 18F or 11C which undergo beta-plus decay and emits a positron (anti-electron). The emitted positron penetrates the object's tissues, where it annihilates with electron from a tissue component. Thereby, the mass of both particles is converted into two or more gamma quanta.
The current PET tomography scanners use annihilation into two gamma quanta having energy of 511 keV and emitted into opposite directions in the electron-positron pair's rest frame. This straight line of gamma quanta emission is referred to as line of response (LOR) and it is reconstructed for each registered event. Current TOF-PET scanners additionally utilize information about time difference between the time-of-flights (TOF) of gamma quanta from the annihilation point to the detectors.
Most of the presently available TOF-PET scanners are capable of registration of the 511 keV gamma quanta by means of inorganic crystal scintillators usually arranged in the form of ring surrounding the diagnosed patient. There are also known TOF-PET solutions (e.g. as disclosed by patent applications WO2011008119 and WO2011008118) in which the gamma quanta are registered using organic plastic scintillators. Events corresponding to the registration of two 511 keV gamma quanta are identified based on the energy deposited in scintillators via photoelectric or Compton effects.
The TOF-PET detectors equipped with dedicated electronics and software enable a reconstruction of positions and times of gamma quanta interaction in scintillator material. This information is then further processed by the appropriate software procedures to reconstruct LOR and TOF for each registered event and next plurality of events are used to determine a metabolic image of the density distribution of radiopharmaceuticals in the patient's body.
Radiopharmaceuticals can in general be divided into two classes distinguished by physical properties of applied isotopes. The first class includes isotopes emitting positrons without subsequent emission of prompt gamma quantum as e.g. 18F which upon emission of positron changes into ground state of 18O. The second class comprises isotopes as e.g. 44Sc or 14O which after emission of positron change into a daughter nucleus in an excited state. The daughter nucleus subsequently de-excites through emission of one or several gamma quanta.
In the current TOF-PET imaging the de-excitation gamma quantum (often referred to as prompt gamma) constitute a source of background since it may give a signal in the detector which can be misclassified as signal from the 511 keV quantum from the electron-positron annihilation. Analogously positron-electron annihilation to the three gamma quanta constitutes a source of unwanted background.
On the other hand the emission of prompt gamma quantum by some of the radio-isotopes may allow for the simultaneous multi-isotope imaging as described e.g. in the patent application WO2012135725. In this application a simultaneous PET imaging with two isotopes one with prompt gamma and one without prompt gamma is disclosed.
Another solutions taking advantage of the registration of the three gamma quanta—two from the positron-electron annihilation and one prompt gamma from the de-excitation of the daughter nucleus—are described e.g. in articles: C. Gringon et al., “Nuclear medical imaging using beta+gamma coincidences from 44Sc radio-nuclide with liquid xenon as detection medium”, Nucl. Instr. Meth. in Phys. Res. A 571 (2007) 142, and P. G. Thirolf, C. Lang, K. Parodi, “Perspectives for Highly-Sensitive PET-Based Medical Imaging Using beta+gamma Coincidences”, Acta Physica Polonica A 127 (2015) 1441. These articles present different methods for registration of the direction and energy of the prompt gamma after Compton scattering in the detector material. This additional information combined with the information from the standard TOF-PET detectors (such as times and positions of the interaction of two gamma quanta from the positron-electron annihilation) results in the improvement of the spatial resolution of the reconstruction of the annihilation point.
Recently it was disclosed a method applicable for determining morphometric images of the living organisms based on positron-electron annihilation into both: two and three gamma quanta and utilising a prompt gamma emitted from the daughter nucleus of the isotope used in the radiopharmaceutical.
This new method of imaging involving registration of three or more annihilation gamma quanta is described in patent application WO2015028604 which discloses procedures of morphometric imaging based on the measurement of the life-time of ortho-positronium.
Orthopositronium (o-Ps) atoms are produced inside cells during the PET imaging. Such atoms, being a bound state of positron and electron may be produced and trapped in the free volumes between molecules. The probability of creation and lifetime of ortho-positronium depends strongly on the size of the free volume and thus it is connected to the morphology of the cells and may be used as an indicator of the stage of development of metabolic disorders. Such correlations have been reported e.g. in article by R. Pietrzak et al., “Influence of neoplastic therapy on the investigated blood using positron annihilation lifetime spectroscopy”, NUKLEONIKA 2013, 58 (1): pp. 199-202.
In vacuum ortho-positronium atom decays predominantly into three gamma quanta, however inside the diagnosed patient it may also disintegrate via emission of two gamma quanta e.g. due to the pick-off process. Therefore, as described in patent application WO2015028604, in order to determine the ortho-positronium life-time image, for each recorded event, a prompt de-excitation gamma is registered in order to determine a time of creation of the positronium atom, and in addition two or three annihilation gamma quanta are registered in order to determine a time of the decay of this atom. An average ortho-positronium annihilation lifetime (τo-Ps) and probability of its production (Po-Ps) determined for each voxel of the image serves as morphological indicators, additional to and independent of the SUV index (Standardised Uptake Value), which in the standard PET imaging expresses the normalized value of the uptake of the radiopharmaceutical in a given voxel of the organism. Combination of indicators SUV, τo-Ps, and Po-Ps is more sensitive to the occurrence of metabolic abnormalities in cells. Therefore, images of the positronium life-time and its creation probability (performed simultaneously with the standard PET images) are very helpful in the medical diagnosis.
In the disclosed patent application WO2015028604 a reconstruction of place and time of positron-electron annihilation into three gamma quanta is performed in following steps:                the imaged space of the object is discretized into voxels, and next        only these voxels are selected which are in the plane defined by points of interaction of annihilation gamma quanta in the detectors, and further on        a χ2(va, ta) statistics is defined as a function of annihilation voxel va and annihilation time ta and the place and time of annihilation is chosen as this for which χ2(va, ta) reaches a minimum of χ2(va, ta), whereby the minimisation is performed over two-dimensional parameters space (va, ta).        
The above described, known in the state-of-the-art procedure, is used as a step for the ortho-positronium image reconstruction and requires a large and variable number of computation operations while searching for the minimum of the χ2 function over a space typically of about (104 voxels)×(3 ns interval).
Therefore, it would be desirable to develop a method allowing for analytical reconstruction of a place of ortho-positronium annihilation into three gamma quanta, which would significantly speed up a reconstruction process, and as a consequence would decrease time needed for the diagnosis of the patient.
It would be also desirable to develop a method enabling determination of the position of ortho-positronium annihilation into three gamma quanta without the necessity of a prior discretization of the image, thus enabling to improve a spatial and temporal resolution of the τo-Ps and Po-Ps morphometric images, and hence improving a quality of diagnosis based on the morphometric imaging.
Moreover, it would be advantageous to develop a method and a device which would allow for multi-tracer imaging, preferably with more than two tracers, thus decreasing significantly the time needed for the sequential imaging which need to be long between subsequent scans because of the long (many hours) biological decay time needed for cleaning up a tracer from the organism. Therefore, imaging with more than two tracers in one day is currently impractical though it could enhance significantly the diagnostic possibilities and would be also of great importance for disentangling regions of production of various beta+ isotopes during hadron-therapy.
It is therefore an object of the present invention to provide a new method for reconstructing the time and place of a positron-electron annihilation into three gamma quanta that reduces significantly a number of calculations to perform with respect to the prior art, and that does not worsen the time and position resolution beyond the instrumental limits of TOF-PET scanners, and to provide a device that applying a said method will permit a simultaneous multi-tracer PET and morphometric imaging with unlimited number of distinct tracers emitting prompt gamma quanta.